Recent studies have led to a total revision of basic perspectives in developmental renal physiology. Earlier functional and anatomical studies indicated that neonatal kidneys operated under conditions of glomerulotubular imbalance, glomerular preponderance and tubular immaturity. However, with modern techniques, it has become apparent that although the neonatal kidney under stress is indeed limited in its capacity to regulate body homeostasis, the neonatal kidney under nonstressful conditions exhibits a careful balance between glomerular and tabular function. Recent work regarding neonatal proximal fluid reabsorption has shown that 1) absolute proximal tubular sodium reabsorption is directly related to single nephron glomerular filtration rate. 2) Proximal tubular reabsorption increases with age as does the surface area of the basolateral membrane and 3) the neonatal proximal tubule appears to be more permeable than that of the adult, possibly the result of a greater "leakiness" across the tight junction. The degree to which variations in permeability of the peritubular membrane might affect fluid transport has not been determined. In this project, we propose to define further forces operating across developing renal proximal tubule cell membranes. We will induce cell swelling in neonatal tubules by blocking active cation transport, measure fluid flux across the peritubular membrane and compare changes in fluid flux with changes in basolateral membrane surface area. We will also estimate the effective intracellular macromolecular osmotic pressure of the developing nephron. These measurements should provide greater insight into developmental changes concerning forces operating across the peritulular membrane and will add to the overall understanding of developmental physiology. Moreover, establishment of this technology will ultimately permit the assessment of basic transport functions in the occasional human specimen of renal tissue that may become available.